Figure 1.

Scrambling pathway of MTCH2

(A) Snapshot from a Martini 3 simulation showing several lipids (colored in yellow, orange, red, magenta, and purple) translocating along the scrambling pathway of MTCH2. The protein is shown as a molecular surface colored according to the character of its residues (hydrophilic = green, hydrophobic = white, positively charged = blue, negatively charged = red). Bulk lipids are depicted as gray beads (phosphate groups) with hydrophobic tails omitted for clarity. Water is represented only schematically as a blue gradient, omitting the presence of water in the cavity of the protein for visual clarity.

(B) Two visualizations of the atomistic structure of MTCH2 after 3 μs of atomistic simulation. Left: Cartoon representation showing α-helices forming the cavity of the protein. Right: Molecular surface representation showing the cavity (colored in orange), the scrambling pathway (dotted magenta line) and the position of the “hydrophobic gate” (red wedges).

(C) More detailed views of the atomistic structure of MTCH2 showing residues of the C-terminal pathway and the “hydrophobic gate.” The structure on the left depicts the frontal and slightly superior view of the MTCH2 cavity. The structure on the right shows MTCH2 rotated counterclockwise by roughly 90° showing frontal view of the C-terminal pathway, while the cavity is mostly hidden. Purple line shows the approximate position of the lipid headgroups in the lower leaflet. The top of the figure represents the cytosol, and the bottom represents the intermembrane space of mitochondria.